Yesterday’s blog post was my first since the onset of the Covid-19 pandemic.  As you’d imagine, the lockdown has delayed PSP clinical trials.  It’s just too risky to patients, caregivers and staff for an older population to make visits to hospital centers for purposes of research on a chronic condition, even one as serious as PSP. 

The drug companies sponsoring these expensive trials want to wait for a major decline in Covid-19 risk in all of the geographically disparate study site locations. They also want to minimize the risk of another wave a few months later interrupting a study and making them start over.  

The clinical trial closest to launch was from the big Belgian company UCB.  It would test intravenous infusions of a monoclonal antibody directed against the tau protein.  You probably know that two such trials, from Biogen and AbbVie, gave negative results last year, with no efficacy but also no serious or frequent toxicity.  Those antibodies were directed at the “N terminal” of tau, meaning the end of the molecule encoded first during the cell’s manufacturing process.  UCB’s antibody, on the other hand, is directed at the “microtubule binding domain,” which is about two-thirds of the way toward the other end.  So it’s worth testing.  That trial will be delayed to April 2021, per UCB’s present plan.

At least a few months behind UCB’s trial is one from a small Swiss company called Asceneuron (pronounced “uh-SEH-nu-ron”).  I’ve discussed it in a previous post. This oral drug inhibits the detachment of a certain type of sugar molecule from tau, reducing its likelihood of misfolding and aggregating.  I haven’t heard when that trial might be starting and I’m sure that the company is playing it by ear. 

A third trial will test an “anti-sense oligonucleotide,” a strand of RNA injected directly into the spinal fluid in the lumbar spine. It circulates around the brain to reduce the production of tau.  A number of companies have ASO programs for tauopathies. There is also early work on ASO molecules small enough to be dosable by mouth, but those are much further from clinical trials.

A company called Retrotope received FDA permission in April 2020 to start testing an oral drug, RT001, to reduce the level of a toxic process in the brain cells called lipid peroxidation. They are testing this approach not only in PSP, but also in multiple other brain disorders where that defect seems to play a role. No word on a start date.

Another approach is an oral drug from the company called Alzprotect that increases production of a protein called progranulin, a neurotrophic factor (i.e., a normally occurring chemical that encourages the growth or repair of brain cells). The drug is AZP2006 and is in a small trial solely to assess safety in 36 patients in France.

Further from a large-scale trial is a non-steroidal anti-inflammatory drug called tolfenamic acid, which is available by prescription in the UK for migraine. Unlike other NSAIDs, it reduces the production of tau and its abnormal phosphorylation. The drug is in an early-phase clinical trial for PSP at the Cleveland Clinic in Las Vegas.

I’ll keep you updated as required.

Hope matters.